Currently, RNA is significantly underutilized as a potential target for drug development: most likely because there exists a lack of basic knowledge about how one should design a molecule to target a folded RNA. In our research, the RNA-binding properties of sidechain-functionalized polyamines are being examined with two important RNA targets: TAR RNA and RRE RNA of HIV. Molecules that bind to these RNAs can potentially shut down replication of the virus. The basic knowledge that will be developed from this work will ultimately be applicable to other RNA targets, and will provide a general set of guidelines for designing molecules that selectively bind a folded RNA structure. Over the past year, we identified a new version of our molecules that binds extremely well to TAR RNA and blocks association of the tat protein. A collaboration with a cell biology group to study the activity of these molecules in HIV infected cells has demonstrated reasonably good activity. We are continuing to optimize the biological activity of our molecules to minimize toxicity and we are pursuing fundamental studies to understand the molecular recognition properties of our molecules for TAR RNA.